Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
Conditions
Interventions
Intervention1: Experimental Arm-1
Dato-DXd IV + Durvalumab IV: Drug- Dato-DXd
- Dato-DXd-6 mg/kg IV on Day 1, Q3W
Drug-Durvalumab
- Durvalumab1120 mg IV on Day 1, Q3W
Approximately 20 cycles or 60
Sponsors
AstraZeneca AB
AstraZeneca Pharma India Ltd
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion Criteria Age 1 Participant must be 18 years at the time of signing the informed consent form ICF. Type of Participant and Disease Characteristics 2 Histologically or cytologically documented locally recurrent inoperable, which cannot be treated with curative intent, or metastatic TNBC. TNBC is defined as: Negative for ER with of tumour cells positive for ER on IHC. Negative for progesterone receptor with 1 of tumour cells positive for progesterone receptor on IHC. Negative for HER2 with 0 or 1 intensity on IHC or 2 intensity on IHC and negative by in situ hybridisation per the ASCO-CAP HER2 guidelines 3 ECOG PS 0 or 1 with no deterioration over the previous 2 weeks prior to randomisation. 4 All participants must provide a FFPE metastatic excluding bone or locally recurrent inoperable tumour sample collected 3 months prior to signing of informed consent ie, start of screening.. 5 PD L1 positive TNBC based on results from an appropriately validated investigational PD L1 22C3 assay CPS 10 from a sponsor-designated central laboratory. 6 No prior chemotherapy or targeted systemic anti-cancer therapy for metastatic or locally recurrent inoperable breast cancer. 7 Eligible for one of the chemotherapy options listed as ICC paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin 8 Has had an adequate treatment washout period before Cycle 1 Day 1, defined as: Major surgery: 3 weeks. Radiation therapy including palliative radiation to chest: 4 weeks palliative radiation therapy to other areas 2 weeks. Corticosteroid therapy for central nervous system CNS metastatic disease: 3 days. Anticancer therapy including hormonal therapy: 3 weeks for small molecule targeted agents: 2 weeks or 5 half-lives, whichever is longer. Chloroquine/hydroxychloroquine: 14 days. 9 Measurable disease by computed tomography CT or MRI as per RECIST 1.1. 10 Adequate bone marrow reserve and organ function within 7 days before Cycle 1 Day 1 as follows 11 Minimum life expectancy of 12 weeks. Sex and Contraceptive/Barrier Requirements 12 Male or female. Reproduction Contraceptive use by females or males should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Exclusion criteria
Exclusion criteria: Exclusion Criteria Medical Conditions 1 As judged by the investigator, any evidence of diseases which, in the investigatorâ??s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol. 2 History of another primary malignancy with exceptions as defined in protocol 3 Persistent toxicities caused by previous anticancer therapy 4 Neoplastic spinal cord compression or active brain metastases 5 Has significant third-space fluid retention and is not amenable for required repeated drainage. 6 Uncontrolled infection requiring IV antibiotics, antivirals or antifungals; suspected infections ; or inability to rule out infections 7 Has active or uncontrolled hepatitis B or C virus infection. 8 Known HIV infection that is not well controlled. 9 Uncontrolled or significant cardiac disease 10 Participant meets one or more of the following, as judged by the investigator: Mean resting corrected QT interval corrected by Fridericiaâ??s formula QTcF 470 ms regardless of gender, obtained from a single 12-lead electrocardiogram ECG performed at screening. History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and/or cause Torsades de Pointes. Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives. 11 Uncontrolled hypercalcaemia 12 History of non-infectious ILD pneumonitis that required steroids, has current ILD pneumonitis, or has suspected ILD pneumonitis that cannot be ruled out by imaging at screening. 13 Has severe pulmonary function compromise. 14 Leptomeningeal carcinomatosis or history of leptomeningeal carcinomatosis. 15 Clinically significant corneal disease. 16 Active or prior documented autoimmune or inflammatory disorders Prior Concomitant Therapy 17 Prior exposure to: a - Any treatment including ADC containing a chemotherapeutic agent targeting topoisomerase I. b - TROP2-targeted therapy. c - Chloroquine/hydroxychloroquine without an adequate treatment washout period of 14 days prior to randomisation. 18 Any concurrent anticancer treatment. 19 Concurrent use of systemic hormone replacement therapy (HRT eg, oestrogen and or progesterone or hormonal contraception. However, concurrent use of hormones for other non cancer related conditions eg, insulin for diabetes is acceptable. 20 Current or prior use of immunosuppressive medication within 14 days prior to randomisation. 21 Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention 22 Major surgical procedure or significant traumatic injury 3 weeks of Cycle 1 Day 1 or an anticipated need for major surgery during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS) assessed by BICR (Blinded Independent Central Review) for Arm 1 Vs Arm 2 PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The comparison will include all randomised participants, as randomized. Timepoint: The primary (and final) PFS analysis for superiority will be performed after approximately 336 BICR PFS events have occurred across the Dato-DXd + durvalumab and ICC + pembrolizumab treatment groups (61% maturity). | — |
Secondary
| Measure | Time frame |
|---|---|
| To demonstrate superiority of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of OS in participants with PD L1 positive locally recurrent inoperable or metastatic TNBCTimepoint: OS is defined as the time from randomisation until the date of death due to any cause.;To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of ORR in participants with PD L1 positive locally recurrent inoperable or metastatic TNBC.Timepoint: ORR is defined as the proportion of participants who have a CR or PR, as determined by the BICR/investigator assessment, per RECIST 1.1.;To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of DoR in participants with PD L1 positive locally recurrent inoperable or metastatic TNBC.Timepoint: DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1, as assessed by BICR/investigator assessment or death due to any cause;To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of PFS as assessed by the investigator in participants with PD L1 positive locally recurrent inoperable or metastatic TNBC.Timepoint: PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator, or death due to any cause.;To evaluate efficacy of Dato-DXd + durvalumab relative to ICC + pembrolizumab by assessment of CBR at 24 weeks in participants with PD L1 positive locally recurrent inoperable or metastatic TNBC.Timepoint: CBR at 24 weeks is defined as the percentage of participants who have a CR or PR or who have SD, per RECIST 1.1, as assessed by BICR/per investigator assessment and derived from the raw tumour data for at least 23 weeks after randomisation.;To assess TTD in breast and arm symptoms in participants treated with Dato-DXd + durvalumab compared with ICC + pembrolizumab.Timepoint: TTD in breast symptoms as measured by the breast symptom | — |
Countries
Argentina, Australia, Brazil, Canada, Chile, China, France, Germany, India, Italy, Japan, Mexico, Peru, Philippines, Poland, Republic of Korea, Singapore, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States of America, Viet Nam
Contacts
Public ContactMr Sandeep AV
AstraZeneca Pharma India Ltd
Outcome results
None listed